E. Engidawork et al., Alteration of caspases and apoptosis-related proteins in brains of patients with Alzheimer's disease, BIOC BIOP R, 281(1), 2001, pp. 84-93
Citations number
56
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Dysregulated programmed cell death or apoptosis Al Alzheimer's disease (AD)
. Caspases, the major effects suggested to be involved in the pathogenesis
of tors of apoptosis, are cysteine proteases that cleave crucial substrate
proteins exclusively after aspartate residues. The activity of caspases are
delicately regulated by a variety of proteins that possess distinct domain
s for protein-protein interaction. To further substantiate the role of apop
tosis in AD, we investigated the levels of nine different proteins involved
in apoptosis by Western blot technique in frontal cortex and cerebellum of
control and AD subjects. The protein levels of caspase-3, -8, and -9, DFF4
5 (DNA fragmentation factor 45), and FLIP (Fas associated death domain (FAD
D)-like interleukin-1 beta -converting enzyme inhibitory proteins) were dec
reased, whereas those of ARC (apoptosis repressor with caspase recruitment
domain) and RICK (Receptor interacting protein (RIP)-like interacting CLARP
kinase) increased in AD. In contrast;, cytochrome c and Apaf-1 (apoptosis
protease activating factor-1) were unchanged. Regression analysis revealed
no correlation between levels of protein and postmortem interval. However,
inconsistent correlation was found between age and levels of proteins as we
ll as among the levels of individual proteins. The current findings showed
that dysregulation of apoptotic proteins indeed exists in AD brain and supp
ort the notion that it may contribute to neuropathology of AD. The study fu
rther hints that apoptosis in AD may occur via the death receptor pathway i
ndependent of cytochrome c. Hence, therapeutic strategies that ablate caspa
se activation may be of some benefit for AD sufferers. (C) 2001 Academic Pr
ess.